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Biomedical subjects

R J Ward

Publications and source records attributed to R J Ward.

At least 145 records · Page 8Linked to original sources
PubMed1988

Mössbauer spectroscopic studies of deproteinised, sub-fractionated and reconstituted ferritins: the relationship between haemosiderin and ferritin.

In a previous study of human haemosiderin and ferritin by a combination of Mössbauer spectroscopy and electron microscopy, it was observed that the Mössbauer spectra of haemosiderin showed a very different temperature dependence to those of ferritin. These differences were related to the superparamagnetic behaviour of small particles of a magnetic material and suggested that the magnetic anisotropy constant of the haemosiderin was considerably larger than that of the ferritin. In the present work, samples of ferritin have been examined by Mössbauer spectroscopy following partial deproteinisation, subfractionation, and reconstitution with and without phosphate, in order to investigate whether these procedures lead to changes in the magnetic anisotropy constant of the iron-containing cores. There is no evidence from the present data that changes in the protein shell, in the size of the iron-containing cores of ferritin, or in the phosphate content lead to any significant changes in the magnetic anisotropy constant, as obtained from the temperature dependence of the Mössbauer spectra. These results indicate that the different magnetic anisotropy constant observed in the case of human haemosiderin resulting from transfusional iron overload must arise from other significant differences in the composition or structure of the iron-containing cores.

Apoferritins↗
PubMed1988

Quantitative analysis of immunogold labelling for ferritin in liver from control and iron-overloaded rats.

The distribution of ferritin antigenicity in control and iron-loaded rat hepatocytes was investigated with an immunogold-ferritin antibody technique. Antibody to horse spleen ferritin showed immunoreactivity as determined by dot blotting with immunogold/silver staining with purified rat liver ferritin but not with rat haemosiderin. The initial site of ferritin degradation was studied by analysing the density of gold labelling in the cytosol and lysosomes in combination with pre-embedding acid phosphatase cytochemistry. Immunoreactive ferritin was present in the cytosol, cytosolic clusters and lysosomes of normal hepatocytes. After iron-loading, the labelling density increased over tenfold in parenchymal cell cytosol with a smaller increase in Kupffer cells. Ferritin clusters contained substantially more immunoreactive ferritin than equivalent areas of lysosomes or cytosol. Analysis of the labelling density in hepatocyte lysosomes showed that, despite a striking increase in iron content, one-quarter of the lysosomes showed less immunolabelled ferritin than the cytosol. The existence of a wide range of ferritin labelling densities in the lysosomes with a large proportion unlabelled suggests that the ferritin protein shell is not degraded at a significant rate either in the cytosol or in clusters but only after incorporation into lysosomes.

Acid Phosphatase↗
PubMed1988

Peer reviewer agreement for major anesthetic mishaps.

In a study of peer reviewer agreement for major anesthetic mishaps, 42 anesthesiologists performed a standardized peer review of 48 reports of anesthetic mishaps obtained from a national data base. The peer review group exhibited agreement (P less than 0.0001) for judgments on the appropriateness of clinical care, the presence or absence of human error, and the role of better monitoring in prevention of the mishap. Personal attributes of the reviewers (eg, type of practice, length of time in practice, and previous experience with mishap review) did not appear to influence agreement. The study findings suggest a highly favorable environment for the development of broadly recognized standards of care in anesthesiology.

Anesthesia↗
PubMed1988

Effects of positional restraint on oxygen saturation and heart rate following exercise.

This report assesses the effects on peripheral oxygen saturation and heart rate that positional restraint induces when a person is prone, handcuffed, and "hog-tied." Peripheral oxygen saturation and heart rate were monitored at rest, during exercise, and during recovery from exercise for 10 adult subjects. The effects of positional restraint produced a mean recovery time that was significantly prolonged. Consequently, the physiological effects produced by positional restraint should be recognized in deaths where such measures are used.

Adult↗
PubMed1988

Unexpected cardiac arrest during spinal anesthesia: a closed claims analysis of predisposing factors.

Fourteen cases of sudden cardiac arrest in healthy patients who received spinal anesthesia were discovered in a preliminary review of 900 closed insurance claims for major anesthetic mishaps. All patients were resuscitated from the intraoperative cardiac arrest, but six suffered such severe neurologic injury that they died in hospital. Of the eight survivors, only one exhibited sufficient neurologic recovery to allow independence in daily self-care. In view of the unexpected nature of the cardiac arrests, as well as the ultimate severity of injury, these cases were analyzed in detail to determine whether there were recurring patterns of management that may have contributed to the occurrence or outcome of these anesthetic mishaps. Two patterns were identified. The first was the intraoperative use of sufficient sedation to produce a comfortable-appearing, sleep-like state in which there was no spontaneous verbalization. Cyanosis frequently heralded the onset of cardiac arrest in patients exhibiting this degree of sedation, suggesting that unappreciated respiratory insufficiency may have played an important role. The second pattern appeared to be an inadequate appreciation of the interaction between sympathetic blockade during high spinal anesthesia and the mechanisms of cardiopulmonary resuscitation. Prompt augmentation of central venous filing through the use of a potent alpha-agonist and positional change might have improved organ perfusion, shortened the duration of cardiac arrest, and lessened the degree of neurologic damage.

Adult↗
PubMed1988

Assessment of trace metal intake and status in a Gujerati pregnant Asian population and their influence on the outcome of pregnancy.

Dietary assessments and biochemical indices including plasma zinc and copper were determined in pregnant vegetarian and non-vegetarian Gujerati women in India at 28 weeks gestation, and the results were contrasted with those of a comparable group of Gujerati pregnant women living in Harrow. Even though the dietary intake of energy, protein and zinc was significantly lower in the Indian vegetarian Gujerati group when compared to the equivalent group in Harrow, the birthweights of the babies delivered at term were similar. The intake of zinc in the diet of the Gujerati Indian vegetarian and non-vegetarian groups was only one quarter of the US recommended intake during pregnancy and was approximately one half in the Harrow Indian groups. Even so, the plasma concentrations of zinc were similar in all dietary groups in either India or Harrow. The albumin content in the plasma of both the Gujerati Indian vegetarian and non-vegetarian was significantly reduced when compared to the equivalent Harrow dietary groups. The plasma concentrations of both calcium and sodium were significantly correlated with the albumin concentration but not with the plasma content of zinc. Copper levels were elevated to the normal range in both dietary groups of the Gujerati and were similar to the concentrations found in the Harrow groups.

Birth Weight↗
PubMed1987

A Mössbauer spectroscopic study of the form of iron in iron overload.

There are major differences in the temperature dependence of the Mössbauer spectra of ferritin and haemosiderin extracted from the organs of humans suffering from transfusional iron overload. Iron overload can also occur in animal systems as a result of artificial treatments or dietary factors. None of the animal systems which were investigated in the present study showed evidence in their Mössbauer spectra for the presence of the haemosiderin found in transfusional iron overload in humans. This suggests that the haemosiderin which occurs in the case of human transfusional iron overload may be specific to that situation.

Animals↗
PubMed1987

Ultrastructural observations in the carbonyl iron-fed rat, an animal model for hemochromatosis.

Rats fed a carbonyl iron-supplemented diet for 4-15 months were studied for iron content and morphologic changes in the liver, spleen, intestinal mucosa, pancreas and heart. All organs had an increased iron content measured by atomic absorption, with the highest concentrations in the liver and spleen. The periportal distribution of stored iron in the liver was similar to that in human hemochromatosis. In animals treated beyond 6 months Kupffer cells and sinusoidal lining cells also showed cytosiderosis. Electron microscopy provided information on ferritin and hemosiderin content and distribution within parenchymal and sinusoidal cells of the liver but no excessive fibrosis was found. Except for the spleen, the other organs showed less iron deposition. Iron-filled lysosomes (siderosomes) were found in macrophages in the intestinal lamina propria and pancreas, as well as in enterocytes, pancreatic acinar cells and heart muscle cells. Heavily iron-laden siderosomes had increased membrane instability which was demonstrated both morphologically and by measurements of latent lysosomal enzyme activities. Even though cirrhosis was not found, the distribution pattern of accumulated storage iron and lysosomal lability indicated that the carbonyl iron-fed rat is a suitable experimental model for human hemochromatosis.

Animals↗
PubMed1987

Fatty acid synthesis and triacylglycerol accumulation in rat liver after chronic ethanol consumption.

1. Liver slices from chronically alcohol-fed rats incubated with 3H2O showed less than half the fatty acid synthesis rates of pair-fed controls. Addition of 50 mmol/l ethanol or of 10 mmol/l lactate and 1 mmol/l pyruvate to the incubation medium did not alter the fatty acid synthesis rates in either groups. Hepatic fatty acid synthesis rates measured in vivo with 3H2O were also significantly reduced in alcohol-fed rats. 2. Time-course experiments showed that after 1 week on the ethanol diet hepatic fatty acid synthesis rates in vitro were similar to control rats, although the liver triacylglycerol content was significantly increased. From the second week of feeding, fatty acid synthesis rates were significantly lower in alcohol-fed rats and the liver triacylglycerol content progressively increased compared with controls. 3. Fatty acid synthase activity in liver cytosolic fractions were similar to controls in the alcohol-fed group after 1 week of feeding but were significantly lower in alcohol-fed rats from the second week onwards. 4. These results indicate that hepatic triacylglycerol accumulation after alcohol feeding is not due to increased fatty acid synthesis. The reduced fatty acid synthesis observed is a consequence of triacylglycerol accumulation.

Animals↗
PubMed1986

Relaxometry of ferritin solutions and the influence of the Fe3+ core ions.

The magnetic field dependence of 1/T1 over the range 0.01 to 50 MHz proton Larmor frequency (NMRD profile) is reported for water protons in solutions of horse spleen apoferritin, and of ferritin reconstituted at both low and high iron levels. The apoferritin results are in every way typical of diamagnetic spherical proteins of their size (K. Hallenga and S. H. Koenig, Biochemistry 15, 4255 (1976)). Titration of up to 24 ferrous ions per protein molecule, with subsequent oxidation to ferric, shows a nonlinear saturating contribution to the NMRD profile which is interpreted as arising from a small number of ferric ions (six to eight) bound close to the outside of each ferritin molecule, and a comparable number of interior sites. The latter become multiply occupied as the core grows and do not contribute measurably to 1/T1 in this state. The former sites are never more than singly occupied, and their contribution to the solvent proton relaxation rates is independent of the loading of the core. Measurements of 1/T2 at 20 MHz are quite in accord with theoretical expectations for apoferritin and ferritin with up to 24 ferric ions per molecule. However, a marked increase in 1/T2 is observed at higher iron loadings that we are unable to account for within the framework of the theory of outer sphere relaxation, even when the effects arising from inhomogeneities in the local magnetic field are included. A sample of human spleen hemosiderin was found to have the same 1/T1 NMRD profile as a comparable sample of ferritin.

Animals↗
PubMed1986

Hemolysis and hyperkalemia complicate malignant hyperpyrexia during anesthetic death.

A healthy, 15-year-old male received a thiopental, nitrous oxide, oxygen, enflurane anesthetic for appendectomy. Cardiac arrest, following succinylcholine administration, was associated with marked hyperkalemia (potassium levels 8.7 to 11.6 meq), hemolysis (hematocrit fall from 41.7 to 26.6%, plasma hemoglobin 27 mg/dL), and creatine phosphokinase (CPK) elevation (8900 units). Vigorous resuscitative therapy including dantrolene was unsuccessful. The diagnosis of malignant hyperthermia was made by the marked CPK elevation on blood samples drawn during resuscitation and analyzed by the Medical Examiner's Office.

Adolescent↗
PubMed1985

The role of iron in ferritin- and haemosiderin-mediated lipid peroxidation in liposomes.

Ferritin and haemosiderin were shown, by the measurement of malondialdehyde production and loss of polyunsaturated fatty acids, to stimulate lipid peroxidation in liposomes. At pH 7.4 ascorbate was additionally required to achieve peroxidation; however, peroxidation occurred at pH 4.5 in the presence of iron-proteins alone. The damage was completely inhibited by the incorporation of chain-breaking antioxidants (alpha-tocopherol and butylated hydroxytoluene) into the liposomes. Metal chelators (desferrioxamine and EDTA) also completely inhibited lipid peroxidation. These and further results indicate that, at pH 4.5, even in the absence of a reducing agent, iron is released from haemosiderin and can mediate oxidative damage to a lipid membrane.

Deferoxamine↗
PubMed1985

Zinc and copper in Asian pregnancies--is there evidence for a nutritional deficiency?

In 92 Hindu Asians, 59% of them vegetarian, and 51 Europeans longitudinal measurements were made during pregnancy of the zinc and copper concentrations in plasma and hair together with urinary zinc excretion, as indices of their zinc and copper status. Maternal diets were assessed once at booking. Zinc intakes ranged from 3.1 to 16.9 mg/day, with average intakes least in vegetarian Hindus and most in Europeans. Average copper intakes ranged between 1.48 and 1.80 mg/day and were similar in the three patient groups. Both ethnic groups showed the pregnancy-associated fall in the plasma concentration of zinc and rise in that of copper but throughout the study Hindus had statistically significant lower levels of zinc and higher levels of copper than Europeans. Urinary zinc excretion was not only significantly lower throughout the study in Hindus than in Europeans but the increase in excretion which occurred after 20 weeks gestation was smaller. There were no ethnic differences in the zinc content of hair. Urinary zinc excretion correlated with both plasma zinc levels and dietary zinc. Mean birthweight in the Hindus was 2912 g and 34% of infants were below the 10th centile, using the Aberdeen standards, compared with 6% of the European babies (mean birthweight 3349 g). No association was found between crude or adjusted birthweight and any of the measures of zinc or copper status in either ethnic group. The Hindus had an apparently lower average zinc status than the Europeans, but there was no evidence that this had acted as a nutritional constraint and was the cause of their slower rate of intrauterine growth.

Adult↗